This invention is in the field of pharmacology, and relates to drug treatments for reducing the dependence of patients on habit-forming and potentially addictive drugs, including narcotics and anti-depressants.
The term "narcotic" as used herein has the same meaning used in standard medical reference works, such as the "more recent" definitions used in Stedman's Medical Dictionary, 26th edition (Williams & Wilkins Publ., Baltimore, 1995) and in the "Analgesics" chapter in the "Drug Evaluations" subscription service published by the American Medical Association (Chicago). Briefly, "narcotics" as used in any definition (either classical or recent) includes: (1) opiate drugs, defined as any preparation or derivative of opium, a natural mixture derived from poppy plants that includes a number of medically important and/or habit-forming or addictive drugs, including morphine, codeine, noscapine, papaverine, thebaine, and heroin; and, (2) opioid drugs, which includes opiates as well as various synthetic narcotic drugs having similar or related chemical structures and effects. Such synthetic narcotics include meperidine (sold under trademarks such as DEMEROL.TM.), hydrocodone (sold under trademarks such as VICODIN.TM.), hydromorphone (sold under trademarks such as DILAUDID.TM.), propoxyphene (sold under trademarks such as DARVON.TM.), oxycodone (sold under trademarks such as PERCODAN.TM. when mixed with aspirin, or PERCOCET.TM. when mixed with acetaminophen), levorphanol, fentanyl, and methadone.
Under a more recent definition that has come to be accepted within the medical profession, the term "narcotics" has been broadened somewhat, to include other synthetic drugs which have "effects that are similar to opium and its derivatives". In order for a drug to be to classified as a "narcotic", its effects must include: (1) the ability to induce "significant alteration of mood and behavior"; (2) the ability to induce a condition of "stuporous analgesia"; and (3) a substantial risk of dependence, tolerance, and/or addiction.
As used herein, the term "narcotic" specifically excludes: (1) barbiturate drugs (which are a separate category of drugs, derived from barbituric acid), even though some barbiturate drugs have many of the same types of effects as narcotics; (2) cocaine and its derivatives, such as crack; and (3) drugs with purely anesthetic or analgesic activity, which do not alter mood or pose a serious risk of addiction and abuse. None of those three categories are relevant to the current invention.
This current invention is limited to methods and compounds for "weaning" a dependent or addicted person from the grip of a habit-forming narcotic drug as defined above (or an anti-depressant drug, as discussed below). This invention involves a drug treatment which can help patients (including patients who have suffered for years from chronic and intractable pain) entirely terminate any subsequent use of a habit-forming narcotic drug.
It is recognized by the Applicant that these same or similar methods and compounds may also be highly useful for helping patients break an addiction to or dependence on barbiturates, cocaine, and certain other addictive or habit-forming drugs which have effects similar to narcotics. Accordingly, the combined drug treatment disclosed herein can and should be evaluated on patients addicted to barbiturates, cocaine, and other addictive drugs. However, the teachings and claims herein do not involve any method of terminating the use of cocaine (or crack, or other cocaine derivatives) or barbiturates, since those two classes of drugs are specifically excluded from the teachings herein.
As is well-known to physicians and other health-care providers, dependence on and addiction to narcotic drugs is a serious and widespread medical and sociological problem. It is also a tragic problem, since most such addictions are triggered not by reckless users who want to get "high" or "stoned". Instead, most people who are addicted to narcotic pain-killers first began using them to help them cope with a serious medical problem that required the use of powerful pain-killing drugs.
As is well-known to physicians and other health-care providers, there is a major need for better methods of helping patients who are "hooked" on narcotics. Currently available methods work some of the times, for some people; however, the struggle to break free of an addiction to, or any long-term use of, a narcotic is a terrible ordeal, even under the best conditions (such as in a professionally-staffed rehabilitation center with full-time living quarters). Although some people manage to break free, usually with the help of on-going support from groups similar to Alcoholics Anonymous, the sad fact is that a majority of all patients who try to break free of a narcotic addiction never fully succeed.
Even among people who are merely "dependent" on narcotics, and who use narcotics to help them cope with chronic severe pain (such as pain caused by cancer or chemotherapy, diabetes, an autoimmune disease, repeated back or neck surgeries, neuropathic or phantom pain, lingering effects of a severe injury or infection, etc.), the side effects caused by narcotics can render life miserable. Such people often must struggle through each day feeling dazed, groggy, and semi-stuporous, as well as frequently nauseous and frequently constipated. They would be extremely relieved and grateful for any treatment that would help them return to a more normal life, where the pain is kept at a tolerably low level while the feelings of dazed grogginess, frequent nausea, constipation, and other side effects of the narcotic are gone.
As used herein, "long-term" use of a narcotic or anti-depressant drug refers to use of such drug by the patient for a sufficiently prolonged period of time to allow the patient to develop a substantial level of dependence on, or addiction to, the narcotic or anti-depressant drug. The method of treatment disclosed herein is designed to help patients break free from such drugs, after they have reached a point where they are unable to stop taking them without substantial medical intervention and assistance.
It is also recognized by the Inventor herein that this same general method (i.e., use of dextromethorphan in conjunction with an oxidase inhibitor) may also be able to help patients avoid the gradual development of dependence on, or addiction to, such habit-forming drugs, when DM plus an oxidase inhibitor are administered in conjunction with an opiate or other narcotic and/or with an anti-depressant, to treat a patient suffering from chronic and intractable pain or another long-term medical problem. Based on various results obtained to date, it is further believed by the Inventor herein that such treatment (i.e., DM plus an oxidase inhibitor in conjunction with a narcotic and/or anti-depressant) is likely to perform better than any and all prior efforts to use dextromethorphan (or other mild NMDA antagonist drugs) in conjunction with narcotics, to reduce the development of dependence on such narcotics. However, that promising form of treatment has not yet been specifically tested and evaluated, and is not addressed or covered by the claims herein.
Prior Use of Dextromethorphan to Potentiate Opiate Drugs
A substantial number of published reports and patents have stated that dextromethorphan, dextrorphan, and other NMDA antagonist drugs can "potentiate" and increase the potency of opiate drugs such as morphine. Accordingly, these reports indicate that using DM in combination with an opiate drug can reduce the dosage of an opiate drug that is required to achieve a desired level of pain-killing efficacy. Some of these reports also suggest that administering DM or another NMDA antagonist drug along with an opiate drug can also help reduce the likelihood that a patient will develop tolerance, dependence, or addiction to the opiate drug. US patents include U.S. Pat. No. 5,321,012 (Mayer et al 1994), U.S. Pat. No. 5,556,838 (Mayer et al 1996), and U.S. Pat. No. 5,654,281 (Mayer et al 1997). Published articles include Koyuncuoglu et al 1992, Trujillo et al 1994, Elliott et al 1994, Advokat et al 1995, Elliott et al 1995, Grass et al 1996, Mao et al 1996, Manning et al 1996, Hoffmann et al 1996, Kauppila et al 1998, and Plesan et al 1998.
However, it appears that all of the above-cited articles involved efforts to merely reduce the dosages of opiates that were required to obtain a satisfactory level of pain-reducing efficacy. Apparently, none of these articles seriously contemplated or proposed that DM, in combination with an entirely different drug that none of those researchers used or tested, might be able to completely and totally break and terminate a dependent or addicted person's need for opiates.
Based on two small-scale studies on heroin addicts in Turkey, it was reported that DM in combination with other drugs such as tizanidine or diazepam might be useful in treating addicts who were suffering withdrawal symptoms (Koyuncuoglu et al 1990 and 1995). However, those articles and a subsequent published letter (Bisaga et al 1997, which reported essentially the same results) apparently did not generate serious attention among other researchers trying to treat heroin addicts.
Just as importantly, none of the patents or articles cited above taught or suggested, in any way, a combination of dextromethorphan with a cytochrome oxidase inhibitor for weaning people from opiates.
Despite all the ongoing efforts to try to help addicts and others who are dependent on or addicted to opiates and other narcotics, there are no adequate and satisfactory ways under the prior art to help opiate users completely terminate their use of opiates and other habit-forming narcotics. A major and important need still exists for improved methods to help people break completely free of dependence on, or addiction to, habit-forming opiates and other narcotics.
It should also be noted that the Applicant/Inventor herein, Richard Smith, is also the inventor or co-inventor on a number of prior US patents involving a combination of dextromethorphan with an oxidase enzyme inhibitor. Those prior US patents include U.S. Pat. No. 5,166,207 (on treating neurological disorders), U.S. Pat. No. 5,206,248 (on treating emotional lability), U.S. Pat. No. 5,350,756 (on treating intractable coughing), U.S. Pat. No. 5,366,980 (on treating dermatitis), and U.S. Pat. No. 5,863,927 (on treating chronic and intractable pain). Smith's research in this field in conjunction with other collaborators is also described in Zhang et al 1992. However, none of those items relate to or suggest the newly discovered use and treatment disclosed herein.
Accordingly, one object of this invention is to disclose a medical treatment involving a certain type of drug combination which can help people break free of dependence on, or addiction to, habit-forming narcotic drugs, so that affected people (including patients who suffer from chronic pain) can completely terminate their use of narcotic drugs.
During the research which led to this invention, it was also discovered that patients who suffered from chronic intractable pain, and who were able to completely terminate their dependence on pain-killing narcotics using a DM/oxidase inhibitor combination, can also, in at least some cases, break free of anti-depressant drugs as well. Accordingly, another object of this invention is to disclose a medical treatment which can help people terminate long-term use of anti-depressant drugs.
These and other objects of the invention will become more apparent through the following summary and description of the preferred embodiments.